Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19.
Adenoviridae
/ immunology
Adenovirus Vaccines
/ immunology
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
COVID-19
/ immunology
COVID-19 Vaccines
/ immunology
Cell Line
Cell Line, Tumor
Female
Genetic Vectors
/ immunology
Gorilla gorilla
/ immunology
HEK293 Cells
HeLa Cells
Humans
Immunogenicity, Vaccine
/ immunology
Macaca
Male
Mice
Mice, Inbred BALB C
Middle Aged
Pandemics
/ prevention & control
SARS-CoV-2
/ immunology
Young Adult
COVID-19
SARS-CoV-2
gorilla adenovirus
immunogenicity
vaccine
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
04 08 2021
04 08 2021
Historique:
received:
06
12
2020
revised:
22
01
2021
accepted:
16
04
2021
pubmed:
26
4
2021
medline:
17
8
2021
entrez:
25
4
2021
Statut:
ppublish
Résumé
The coronavirus disease 2019 (COVID-19) pandemic caused by the emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health, and there is an urgent need to develop safe and effective vaccines. Here, we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV-2. We show that our vaccine candidate, GRAd-COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies that neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, T helper (Th)1-dominated cellular response. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV-2-neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at a massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of the GRAd-COV2 vaccine in a currently ongoing phase I clinical trial (ClinicalTrials.gov: NCT04528641).
Identifiants
pubmed: 33895322
pii: S1525-0016(21)00210-0
doi: 10.1016/j.ymthe.2021.04.022
pmc: PMC8062434
pii:
doi:
Substances chimiques
Adenovirus Vaccines
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Banques de données
ClinicalTrials.gov
['NCT04528641']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2412-2423Informations de copyright
Copyright © 2021 The American Society of Gene and Cell Therapy. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests S. Capone, A.R., M.G., S.B., A.S., A.M.C., R.S., F.B., A. Leuzzi, E.L., G. Miselli, A.N., M.F., F.T., M.S., A.F., S. Colloca, and A.V. are employees of ReiThera Srl. A.F. and S. Colloca are also shareholders of Keires AG. A. Lahm is a consultant for ReiThera Srl. S. Colloca, A. Lahm, A.R., and A.V. are inventors of the patent application number 20183515.4, titled “Gorilla Adenovirus Nucleic Acid- and Amino Acid-Sequences, Vectors Containing Same, and Uses Thereof.” The other authors declare no competing interests.